Sepsis, An Undercover Killer

Severe sepsis is a raging infection that shuts down organs. It is important to find it fast, but that can be tricky.

Dr. Green is Clinical Research Fellow, Department of Emergency Medicine, University of California, Davis School of Medicine.

Severe sepsis is a common but deadly condition. It is usually caused by a bacterial infection that sets off a body-wide inflammatory response. It can show up in a number of ways. A patient might appear in the ER with an altered body temperature – typically higher than 100.4° F (38° C) or lower than 96.8° F (38° C), rapid heartbeat, rapid breathing, or lab tests showing signs of an infection (lots of white blood cells) or unusually few white cells.

Even more disturbing is the fact that the volume of patients presenting to hospitals with sepsis appears to be increasing, making it increasingly difficult for doctors to quickly identify these patients and determine how severe their sepsis is.

The leading cause of death in U.S. hospitals, severe sepsis is associated with an estimated in-hospital mortality risk between 25 and 30%. In the U.S. alone, more than 500,000 adult patients are admitted to hospitals every year with evidence of sepsis and organ dysfunction. Each year in the United States there are approximately 750,000 cases of severe sepsis, which result in 215,000 deaths.

Even more disturbing is the fact that the volume of patients presenting to hospitals with sepsis appears to be increasing, making it increasingly difficult for doctors to quickly identify these patients and determine how severe their sepsis is.

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Some relatively new techniques have shown a lot of promise in the treatment of severe sepsis. For example, Early Goal Directed Therapy (EGDT), which involves intense monitoring of oxygen delivery to the patient, can resuscitate patients and reduce the risk of mortality in people with dysfunctions of the heart or other organs. The benefit of these newer methods decreases however, if there is any delay in beginning them, which makes it essential for doctors to determine which patients are at the highest risk and for patients and families to be alert to the symptoms.

Why Is Sepsis So Dangerous?

A person can develop sepsis when the body – in particular, the bloodstream – is overwhelmed with bacteria. The infection can begin anywhere in the body, but common places are the intestines, kidneys, lungs (as in pneumonia), or the linings around the brain (as in meningitis).

Symptoms of severe infection typically include chills, fever, confusion, rash, and shaking. The most dangerous symptom of sepsis is a rapid drop in blood pressure, which can cause a patient to go into shock, which is life-threatening since the organs, including the brain, are deprived of oxygen. Treatment involves giving antibiotics through an IV, and administering fluids, oxygen, and medications to bring blood pressure back up. Sometimes a breathing machine or dialysis may be needed if the lungs or kidneys are affected.

Determining A Person’s Risk Early on Saves Time, Money, and Lives

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Because of the seriousness of sepsis and the possibility of shock, it is critical for doctors to determine each patient’s risk level, so that he or she may be treated quickly and appropriately. More than 50% of patients with severe sepsis receive some part of their care in an intensive care unit (ICU), and sepsis is the most common cause of ICU admissions (other than surgery) in the United States.

Because of the seriousness of sepsis and the possibility of shock, it is critical for doctors to determine each patient’s risk level, so that he or she may be treated quickly and appropriately.

Treating severe sepsis contributes significantly to the overcrowding of ICUs, and adds to the more than $16 billion annual cost of caring for this syndrome in the United States. As the United States population ages, the number of severe sepsis cases will inevitably increase. Accurate methods to determine a person’s risk could focus our limited healthcare dollars on seriously ill patients who are most likely to benefit, and at the same time decrease the use of invasive procedures on patients who have lower risk. Here, we’ll outline some of the newer techniques that doctors use to figure out who’s at greater risk for sepsis and who is not.

Organ Dysfunction

Sepsis can affect one or many organs of the body, depending on the extent of the infection. Doctors determine whether organs are failing using basic clinical evidence that is fairly clear-cut, and doing so can tell them who is at risk for death in the short term. However, patients with severe sepsis can range from having several failing organs to more mild organ “malfunctions.” Therefore, there are limits to what organ function – or organ failing – can tell us about the health status of the patient in question. For this reason, doctors have to use additional techniques that help them flesh out the picture when a patient develops sepsis.

Tests, Tests, and More Tests

There are a number of tests, some newer than others that are used to determine whether sepsis is present and, if it is, the degree to which it is present.

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The Acute Physiology and Chronic Health Evaluation (APACHE) tests were the earliest ways to determine risk for septic patients in the ICU. But they are complex, and can often require information that’s not typically available early on in treatment such as data on the oxygen pressure in arterial blood. The Mortality in Emergency Department Sepsis (MEDS) score is used for adult patients who come into the emergency department with a suspected infection. This tool was developed specifically for determining risk quickly, using basic factors, which makes it very useful for measuring risk in the early stages and in many different types of patients. Unfortunately, its accuracy is not always so high in patients with severe sepsis, so it may needed to be used along with other tests.

Other methods, like the Rapid Emergency Medicine (REMS) and the Confusion Urea Nitrogen Respiratory Rate Blood Pressure Age over 65 (CURB-65) can be used in adult patients with a suspected infection, but again, their use in people with severe sepsis is not so well indicated. One test that can work well in severe sepsis is the Sequential Organ Failure Assessment (SOFA), which measures the degree of organ dysfunction and can predict whether critically ill patients will respond to treatment.

Finally, for patients with suspected sepsis, we now have the Predisposition, Infection, Response, Organ (PIRO) Dysfunction Staging System. This method uses several factors of the patient’s presentation such as history of chronic liver disease or heart failure, combined with his or her inflammatory response, and can be measured in both ICUs and ERs. All of these methods have their benefits, but PIRO is one of the most useful ways to determine one’s risk, especially in non-ICU settings, where doctors may not have access to a wide variety of lab tests and diagnostic equipment.

Blood Markers Can Predict Risk, But Should be Combined

Lactate Levels Can Gauge Severe Sepsis

The level of lactic acid (or lactate) in the blood is well known to predict mortality in people who have sepsis. Lactate is produced when the body breaks down carbohydrates: most people are aware of it as being higher after strenuous exercise.

One big benefit of using lactate levels to determine mortality risk is that it can help evaluate sepsis regardless of whether the organs are in good or bad shape.

But lactate can also be present in high levels during infection, which makes it helpful in evaluating sepsis. High lactate in the body can signal to doctors that the EGDT measure should be used to optimize oxygen levels in the blood. One big benefit of using lactate levels to determine mortality risk is that it can help evaluate sepsis regardless of whether the organs are in good or bad shape. Doctors will often take a series of lactate tests to improve their accuracy: depending on how lactate levels “behave,” they can tell whether mortality risk is getting higher or lower. The drawback of using lactate levels to determine mortality risk is that lactate can be elevated for different reasons – and complicating this is the fact that sometimes people with severe sepsis can have normal lactate levels. Therefore, using these tests in conjunction with others (for example, of inflammatory biomarkers in the blood) can be extremely helpful to clinicians.

Using Biomarkers to Predict Risk: Interleukin-6 and Procalcitonin

When the body is under “attack” by an invader (bacteria or virus), the immune system kicks into high gear. One of the molecules that helps regulate the immune response is interleukin-6 (IL6), and is at its highest levels just two hours after infection sets in. For this reason, IL6 levels can be helpful in predicting mortality risk when people have sepsis, especially over time, rather than early on. However, since IL6 levels aren’t always available in labs, its use can be limited.

Procalcitonin is another molecule that can help predict mortality from sepsis. It, too, rises when the body is under attack by a pathogen, often a bacterium. It is so good at predicting the presence of infection that it generally outperforms other inflammatory biomarkers. It can be helpful in predicting mortality risk in a many different types of cases, and both in the ICU and ER.

Combining Methods and Getting Closer to the Goal

There is good evidence that using a combination of tests is the most effective way to predict the severity of sepsis, and its associated risk of death. Lactate has its benefits and drawbacks, as discussed, as do inflammatory biomarkers in the blood. For these reasons, using lactate levels alongside inflammatory biomarker tests increases their accuracy considerably. The more information doctors can gather about what is going on inside the body, by using a range of techniques, the better equipped they’ll be to make a diagnosis and determine the best course of treatment.

Of course, preventing sepsis from developing in the first place is best by maintaining rigorous hygiene after surgery and monitoring wounds, for example. But barring this, sepsis should be treated quickly and accurately.

Severe sepsis is a common but deadly condition that carries with it a serious risk of mortality. Identifying the condition early is key. Quick identification and treatment can significantly decrease the death risk for sepsis patients. There are many methods that doctors use to identify patients with sepsis and determine how severe it is, and they all have their benefits and drawbacks. The most powerful methods involve the combination of different tests – for example, checking lactate levels alongside inflammatory biomarkers – in order to boost their predictive power.

Of course, preventing sepsis from developing in the first place is best by maintaining rigorous hygiene after surgery and monitoring wounds, for example. But barring this, sepsis should be treated quickly and accurately. Given the fact that so many people suffer from sepsis each year, developing better, stronger methods to evaluate its presence and severity will be a continuing goal in research.